P. carinii is the fungus that causes P. carinii pneumonia (PCP) in people with depressed immune systems such as AIDS patients, patients undergoing chemotherapy, or transplant patients being treated with immunosuppressants. The currently used drugs that seem most effective are pentamidine and the combination of trimethoprim and sulfamethoxazole. These treatments have severe side effects and the mortality rate remains high. Thus, alternative, more successful treatments for this condition are needed.
A known characteristic of P. carinii is that it has an absolute requirement for S-adenosylmethionine (AdoMet) and is unable to synthesize this compound. It apparently scavenges this material from the blood of the infected host. See, Merali, S., et al., J. Biol. Chem. (2000) 275:14958-14963. By depleting methionine concentration in the blood, the availability of AdoMet in the blood is also depleted, thus inhibiting the infectious agent.
The uptake of AdoMet by P. carinii is verified by the inverse correlation of the level of infection and plasma levels of AdoMet in infected subjects. See, Skelly, M., et al., Lancet (2003) 361:1267-1277. Thus, the levels of AdoMet in plasma may be used as a diagnostic method for this infection.
The use of L-methionine-α-deamino-γ-mercaptomethane lyase (methioninase, METase) for the treatment of methionine-dependent tumors, the production of recombinant METase, and modification of METase to reduce antigenicity and enhance half-life by coupling to a polymer such as polyethylene glycol have been described previously in U.S. Pat. Nos. 6,231,854; 6,461,851; 5,888,506; 5,690,292; 5,891,704; and 5,715,835, all incorporated herein by reference. In addition, the use of expression of the gene-encoding methioninase for tumor treatment is described in U.S. Pat. No. 6,524,571, also incorporated herein by reference. According to the present invention, methioninase, optionally in combination with additional antibiotics, is employed in the control of P. carinii infection.